Co-administration of Bedaquiline and Lopinavir/ Ritonavir should be avoided due to exposure to Bedaquiline being twice as high when co-administered. This could enhance the toxicity of bedaquiline.
Lopinavir/Ritonavir versus Bedaquiline
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Study Design
Concomitant use of bedaquiline (single 400 mg dose) with the fixed combination of lopinavir and ritonavir (LPV/R; 400 mg/ 100 mg twice daily for 24 days) in healthy individuals
Study Results
increased the AUC of bedaquiline by 22%; mean peak plasma concentrations of bedaquiline were not substantially affected; clinical importance is unknown.
using geometric mean ratios, when HIV-infected patients (n=10) who were stable on LPV/r - based treatment received bedaquiline 400 mg once daily for 2 weeks, followed by 200 mg 3 times weekly for 22 weeks, the AUC [95% CI] was increased by 72% [16%, 155%] compared with patients who received bedaquiline alone (p= 0.009).
Study Conclusions
Bedaquiline and LPV/r should be used concomitantly with caution and only if potential benefits outweigh risks. DHHS guidelines recommended that patients be monitored for QT interval prolongation and liver dysfunction.
References
Pandie M, Wiesner L, McIlleron H, Hughes J, Siwendu S, Conradie F, Maartens G. Drug–drug interactions between bedaquiline and the antiretrovirals lopinavir/ritonavir and nevirapine in hiv-infected patients with drug-resistant tb. Antimicrobial Agents And Chemotherapy . 2016; 4: 1037-1040.
Lopinavir/Ritonavir versus Bedaquiline
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Study Design
Parallel-group pharmacokinetic study in adults 18 years and older who received bedaquiline monotherapy (bedaquiline 400mg once daily for 2 weeks, followed by 200mg three times weekly; n is 17), co-administered with nivirapine-based ART (on for more than 2weeks; n is 17), or lopinavir/ritonavir-based ART (on for more than 3 days; n is 14).
Study Results
Median bedaquiline PK parameters were significantly higher in the bedaquiline co-administered with lopinavir/ritonavir group vs. bedaquiline monotherapy group: AUC(0-48h) (67002 vs. 34730ng.h/mL; P is 0.003; Cmax (1970 vs. 2235 ng/mL; P is 0.234) Tmax (6 vs. 4 hours; P is 0.003); and t1/2 (55 versus 31 hours; P is 0.004). On multivariate analysis, bedaquiline exposure was increased by 62 when co-administered with lopinavir/ritonavir (P is 0.010; 95 CI 13-132).
Study Conclusions
Lopinavir/ritonavir significantly increases the exposure of bedaquiline and should be used with caution. The clinical significance is yet to be determined, but close monitoring is recommended if other options are not available.
References
Pandie, M, Wiesner, L, Mcllleron, H, Hughes, J, Siwendu, S, Conradie, F, Variava, E, Maartens, G. Drug-drug interactions between bedaquiline and the antiretrovirals lopinavir/ritonavir and nevirapine in hiv-infected patients with drug-resistant tb. Journal Of Antimicrobial Chemotherapy. 2016; 4: 1037-1040.
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